Attention has been drawn to vitamin A as being an effective ingredient for preventing or treating keratoses such as of the cornea and conjunctiva and also of the skin mucosa. On the other hand, vitamin A that is a lipophilic vitamin is very sensitive to air, light, heat, acids, metal ions and the like and is particularly very unstable in aqueous solutions, with a difficulty involved in stably formulating it in ophthalmic compositions such as eye drops and the like.
For techniques of stabilizing such unstable vitamin A, there have been hitherto proposed a method of stabilization with nonionic surfactants such as polyethylene hardened castor oil and the like (see, for example, JP-A H05-331056: Patent Document 1), a method of stabilization with vitamin Es that are a hydrophobic antioxidant (see, for example, JP-A H06-247853: Patent Document 2), and a technique of stabilization from the aspect of a container or package (see, for example, JP-A H06-40907: Patent Document 3, and JP-A 2003-113078: Patent Document 4), and a stabilization technique wherein preparation is carried out by high-energy emulsification (see, for example, JP-A 2002-332225: Patent Document 5). However, the prior-art techniques have not been well satisfactory with respect to the level of stability necessary for medical products in high concentration systems (of not lower than 50,000 units). In view of the above, there has been demanded a technology of further increasing the stabilization of vitamin A in ophthalmic compositions formulated with a high concentration of vitamin A.